A study by the Universities of Sussex and Portsmouth in the UK reveals that horses can read and then remember people’s emotional expressions, enabling them to use this information to identify people who could pose a potential threat. Published on April 26, 2018, in Current Biology, the paper “Animals Remember Previous Facial Expressions That Specific Humans Have Exhibited” is authored by a team of psychologists, co-led by Professor Karen McComb, from the University of Sussex, and Dr. Leanne Proops, from the University of Portsmouth – both specialists in animal behavior. The research team conducted controlled experiments in which domestic horses were presented with a photograph of an angry or happy human face and several hours later saw the actual person who had exhibited the expression, now in an emotionally neutral state. This short-term exposure to the photograph of a person’s facial expression was enough to generate clear differences in subsequent responses upon meeting that individual in the flesh later the same day. The study found that despite the humans being in a neutral state during the live meeting, the horses’ gaze direction revealed that they perceived the person more negatively if they had previously seen them looking angry in the photograph rather than happy. Previous research, including at University of Sussex, has shown that animals tend to view negative events with their left eye due to the right brain hemisphere’s specialization for processing threatening stimuli (information from the left eye is processed in the right hemisphere). Importantly, in the current experiment, the humans did not know which photographs the horses had previously seen, to avoid any risk of behaving differently themselves.
Doctors could be a step closer to finding the most effective way to treat cancer with a double whammy of a virus combined with boosting the natural immune system, according to a pioneering study by researchers at The University of Texas Health Science Center at Houston (UTHealth) and The Ohio State University. “The findings of this research are very exciting because it helps unravel the complex yin and yang relationship between the natural cancer-fighting power intrinsic to our immune system and externally added cancer-killing cells that are given as a therapy. It’s very significant because it shows, contrary to recent scientific claims, that virotherapy can be combined with cell therapy for a positive effect,” said the study’s corresponding author Balveen Kaur, PhD, Professor and Vice Chair of Research in the Vivian L. Smith Department of Neurosurgery at McGovern Medical School at UTHealth. Previous scientific wisdom has discredited combining virotherapy and externally added natural killer (NK) cell therapy to the body’s NK cells, but there could be clear cancer-fighting benefits – if sufficient external NK cells are deployed to destroy the tumor and stop its spread, as revealed in the paper that was published online on April 23, 2018 in PNAS. The article is titled “Complex Role of NK Cells in Regulation of Oncolytic Virus–Bortezomib Therapy.” To reach this conclusion, physicians devised a mathematical formula unlocking the complex interactive relationship between externally introduced viruses and NK cells in addition to the immune system’s existing NK cells to calculate cancer cell-killing potency. The mathematical modeling was able to predict how a virus-treated tumor would respond to NK cell therapy, depending on the number of NK cells introduced to the tumor.
Scientists examining the genome of Egyptian fruit bats, a natural reservoir for the deadly Marburg virus, have identified several immune-related genes that suggest bats deal with viral infections in a substantially different way than primates. Their research, published online on April 26, 2016 Cell, demonstrates that bats may be able to host viruses that are pathogenic in humans by tolerating–rather than overcoming–the infection. The article is titled “The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity.” Bats are known to harbor many viruses, including several that cause disease in humans, without demonstrating symptoms. To identify differences between antiviral mechanisms in humans and bats, the research team sequenced, assembled, and analyzed the genome of Rousettus aegyptiacus, the Egyptian fruit bat–a natural reservoir of Marburg virus and the only known reservoir for any filovirus. Jonathan Towner, PhD, of the Viral Special Pathogens Branch at the Centers for Disease Control and Prevention (CDC), provided the bats from which the DNA was extracted. Dr. Towner had traveled to Uganda to investigate the colony of Egyptian fruit bats implicated in a Marburg fatality there. “Using that DNA, we generated the most contiguous bat genome to date and used it to understand the evolution of immune genes and gene families in bats. This is classical comparative immunology and a good example of the link between basic and applied sciences,” explained co-senior author Gustavo Palacios, PhD, who heads the Center for Genome Sciences at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). In the process, Dr. Palacios and colleagues at the CDC and Boston University made some striking findings.
A global research project has mapped out the genetic basis of major depression, identifying 44 genetic variants which are risk factors for depression, 30 of which are newly discovered. The study, by the Psychiatric Genomics Consortium, and co-led in the UK by King’s College London, is the largest study to-date of genetic risk factors for major depression. Published online on April 26, 2018 in Nature Genetics, the research finds that the genetic basis for major depression is shared with other psychiatric disorders such as schizophrenia, and that all humans carry at least some of the 44 genetic risk factors identified in the study. The article is titled “Genome-Wide Association Analyses Identify 44 Risk Variants and Refine the Genetic Architecture of Major Depression.” A significant number of the genetic variants identified in the study are directly linked to the targets of current antidepressant medications. Analysis of the data also suggests that having a higher body mass index (BMI) is linked to an increased risk of major depression. Previous studies have struggled to identify more than a handful of genetic variants associated with depression. By combining seven separate datasets, the research team included data on more than 135,000 people with major depression and more than 344,000 controls. The study was an unprecedented global effort by over 200 scientists who work with the Psychiatric Genomics Consortium, and was led by the University of North Carolina School of Medicine and the University of Queensland in Australia. Professor Cathryn Lewis and Dr. Gerome Breen of King’s College London led the UK contribution, along with scientists and psychiatrists from the Universities of Edinburgh, Cardiff, and University College London (UCL).
A new study has cast doubt on leading theory for how tiny creatures have evolved for tens of millions of years – without ever having sex. Most animals reproduce sexually, a process which shuffles genes from parent to offspring. This makes natural selection more efficient and allows animals to evolve defenses against changing environmental conditions more rapidly, especially new diseases. Bdelloid rotifers however appear to be an exception to this rule: they are all female, and their offspring are clones of their mothers. Bdelloids are microscopic animals that live in freshwater and damp habitats across the world. Despite their apparent lack of sex, we know they have evolved for tens of millions of years into more than 500 species. By studying their genomes – the set of all the genes that define an animal’s characteristics – researchers thought they had identified an explanation for how bdelloids had ‘gotten away’ with no sex for millions of years. However, a new study, published online on April 24, 2018 in PLOS Biology and led by Imperial College London researchers, reveals this mechanism may not be the main explanation for the bdelloids’ success. The article is titled “Comparative Genomics of Bdelloid Rotifers: Insights from Desiccating and Nondesiccating Species.” Many species of bdelloid endure periods of drying out, called desiccation. Although they survive desiccation, the process damages their DNA, which they need to repair when rehydrated. Based on results of a previous study of the genome of a species that survives desiccation, researchers had proposed that the repair of DNA might remove some of the problems of being asexual, for example by removing harmful mutations and possibly allowing occasional recombination of genes to occur.
New research shows there might be health benefits to eating certain types of dark chocolate. Findings from two studies being presented at the Experimental Biology 2018 annual meeting in San Diego (April 21-25) show that consuming dark chocolate that has a high concentration of cacao (minimally 70% cacao, 30% organic cane sugar) has positive effects on stress levels, inflammation, mood, memory, and immunity. While it is well known that cacao is a major source of flavonoids, this is the first time the effect has been studied in human subjects to determine how it can support cognitive, endocrine, and cardiovascular health. Lee S. Berk, DrPH, Associate Dean of Research Affairs, School of Allied Health Professions and a researcher in psychoneuroimmunology and food science from Loma Linda University, served as principal investigator on both studies. “For years, we have looked at the influence of dark chocolate on neurological functions from the standpoint of sugar content – the more sugar, the happier we are,” Dr. Berk said. “This is the first time that we have looked at the impact of large amounts of cacao in doses as small as a regular-sized chocolate bar in humans over short or long periods of time, and are encouraged by the findings. These studies show us that the higher the concentration of cacao, the more positive the impact on cognition, memory, mood, immunity, and other beneficial effects.” The flavonoids found in cacao are extremely potent antioxidants and anti-inflammatory agents, with known mechanisms beneficial for brain and cardiovascular health.
It’s DNA, but not as we know it. In a world first, Australian researchers have identified a new DNA structure – called the “i-motif” – inside cells. A twisted “knot” of DNA, the i-motif has never before been directly seen inside living cells. The new findings, from the Garvan Institute of Medical Research, were published online on April 23, 2018 in Nature Chemistry. The article is titled “I-Motif DNA Structures Are Formed in the Nuclei of Human Cells.” Deep inside the cells in our body lies our DNA. The information in the DNA code – all 6 billion A, C, G, and T letters – provides precise instructions for how our bodies are built, and how they work. The iconic “double helix” shape of DNA has captured the public imagination since 1953, when James Watson and Francis Crick famously uncovered the structure of DNA. However, it’s now known that short stretches of DNA can exist in other shapes, in the laboratory at least – and scientists suspect that these different shapes might play an important role in how and when the DNA code is “read.” The new shape looks entirely different from the double-stranded DNA double helix. “When most of us think of DNA, we think of the double helix,” says Associate Professor Daniel Christ (Head, Antibody Therapeutics Lab, Garvan) who co-led the research. “This new research reminds us that totally different DNA structures exist – and could well be important for our cells.” “The i-motif is a four-stranded ‘knot’ of DNA,” says Associate Professor Marcel Dinger (Head, Kinghorn Centre for Clinical Genomics, Garvan), who co-led the research with Assistant Professor Christ.
Competitive breath-hold divers have only two options to increase their time underwater – through training, they can try to boost their lung capacity or increase their red blood cell count. Over hundreds, if not thousands of years, however, a group of Southeast Asian “sea nomads” known for their deep-diving prowess has evolved a better solution: larger spleens. The spleen holds oxygenated red blood cells, so presumably an enlarged spleen (those of the sea nomads, or Bajau people, are about 50 percent larger than the spleens of unrelated, non-diving neighboring groups) injects more blood cells into the circulation and makes more oxygen available for basic body functions during prolonged dives. The physical and genetic changes that have enabled the Bajau to dive longer and deeper is yet another example of the immense variety of human adaption to extreme environments, in this case, environments with low levels of oxygen, said Dr. Rasmus Nielsen, a Professor of Integrative Biology at the University of California, Berkeley. These examples can be key to understanding human physiology and human genetics. “We can’t really make experiments in humans, where we expose people to new conditions and have controlled genetic experiments in the same way we can do in fruit flies and mice,” Dr. Nielsen said. “But nature has made experiments for us that tell us how humans react and adapt genetically to a whole new set of physiological conditions, so that we can explore and learn much more about the interaction between genetics and physiology.” The surprise finding led researchers from the University of Copenhagen and UC Berkeley to a genetic mutation that appears to have spread throughout the population to increase spleen size. This genetic variant upregulates thyroid hormone, which in mice has been linked to larger spleen size.
To get the extra energy they need to fuel their uncontrolled growth, cancer cells break down some of their own parts for fuel – a process known as autophagy, or “self-eating.” Researchers from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center found a possible therapeutic strategy to block self-eating in one of the deadliest cancers, as well as to cut off the tumor’s other energy sources. The researchers are reporting preclinical findings for a potential two-treatment strategy to block multiple mechanisms of cancer cell metabolism in pancreatic cancer at the American Association for Cancer Research (AACR) Annual Meeting in Chicago. The findings were presented on April 18, 2018. “We know that cancer cells have a greater need for energy than normal cells,” said UNC Lineberger’s Channing Der (photo), PhD, Sarah Graham Kenan Distinguished Professor in the UNC School of Medicine Department of Pharmacology. “They get their energy by changing normal metabolic processes to allow them to generate more energy, and one of these processes is self-eating. Basically what a cancer cell does is it does this more efficiently than a normal cell.” In other studies, pancreatic cancer cells have been known to rely more heavily on autophagy, but UNC Lineberger scientists reported evidence that a type of treatment — an ERK inhibitor — actually increased their reliance on this. The researchers believe the compound prevents the cell from relying on other energy sources, driving it toward autophagy. “The cancer cell has many ways to achieve what it wants in terms of getting more energy,” Dr. Der said. “We find that if you try to stop one, a cancer cell has the ability to compensate. I think the analogy many of us use is the ‘whack-a-mole’ concept where you knock one thing down, and something else pops up.
(by Rachel DeRita, PhD Candidate,Thomas Jefferson University, Department of Cancer Biology). The Abramson Cancer Center at the University of Pennsylvania (UPenn) continues to make innovative advancements in the field of cancer immunotherapy in the midst of what has been called the “immune revolution” by the cancer center’s director, Robert H. Vonderheide (photo), MD, PhD. He explains that the success with the revolutionary immune system-based therapies is “bittersweet,” as many patients are either non-responsive or re-lapse after initial success. A main strategy of the current cancer immunotherapies is to block the immune system’s “off switch.” For example, when the molecule PD-1 on immune cells is bound to PD-L1 on tumor cells, the immune system deactivates and allows the cancer to hide from the immune system. Antibodies against PD-1 (pembrolizumab, brand name Keytruda) can block the deactivation caused by PD-1/PD-L1 binding, and are approved for the first-line treatment of metastatic non-small cell lung cancer with overexpression of PD-L1. Approximately 30% of patients to not respond to this treatment and another 25% exhibit further tumor progression after one year. The search for improvements to current immunotherapies has led to a new class of immunotherapy drugs known as monoclonal antibodies to a protein called CD40. CD40 is expressed by the antigen-presenting cells of the immune system, which are responsible for eliciting an anti-tumor response. When CD40 is bound by other surface markers on T-helper cells, the antigen-presenting cell (such as a B cells or dendritic cells) is activated to perform a number of functions to eventually target and kill tumor cells. By stimulating this molecule with an antibody, the anti-tumor response is strengthened. Dr.